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Advanced Healthcare Materials Nov 2023Previous parathyroid hormone (PTH)-related peptides (PTHrPs) cannot be used to prevent implant loosening in osteoporosis patients due to the catabolic effect of local...
Previous parathyroid hormone (PTH)-related peptides (PTHrPs) cannot be used to prevent implant loosening in osteoporosis patients due to the catabolic effect of local sustained release. A novel PTHrP (PTHrP-2) that can be used locally to promote osseointegration of macroporous titanium alloy scaffold (mTAS) and counteract implant slippage in osteoporosis patients is designed. In vitro, PTHrP-2 enhances the proliferation, adhesion, and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) within the mTAS. Further, it promotes proliferation, migration, angiogenesis-related protein expression, and angiogenesis in human umbilical vein endothelial cells (HUVECs). Compared to PTH(1-34), PTHrP-2 can partially weaken the osteoclast differentiation of RAW 264.7 cells. Even in an oxidative stress microenvironment, PTHrP-2 safeguards the proliferation and migration of BMSCs and HUVECs, reduces reactive oxygen species generation and mitochondrial damage, and partially preserves the angiogenesis of HUVECs. In the Sprague-Dawley (SD) rat osteoporosis model, the therapeutic benefits of PTHrP-2-releasing mTAS (mTAS ) and ordinary mTAS implanted for 12 weeks via micro-CT, sequential fluorescent labeling, and histology are compared. The results demonstrate that mTAS exhibits high bone growth rate, without osteophyte formation. Consequently, PTHrP-2 exhibits unique local synthesis properties and holds the potential for assisting the osseointegration of alloy implants in osteoporosis patients.
Topics: Rats; Animals; Humans; Osseointegration; Parathyroid Hormone-Related Protein; Titanium; Rats, Sprague-Dawley; Osteogenesis; Alloys; Endothelial Cells; Osteoporosis; Printing, Three-Dimensional
PubMed: 37584445
DOI: 10.1002/adhm.202301604 -
Bone & Joint Research Jul 2023Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and...
Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.
PubMed: 37394235
DOI: 10.1302/2046-3758.127.BJR-2022-0310.R1 -
Nature Communications Feb 2024Osteoarthritis (OA) is a progressive and irreversible degenerative joint disease that is characterized by cartilage destruction, osteophyte formation, subchondral bone...
Osteoarthritis (OA) is a progressive and irreversible degenerative joint disease that is characterized by cartilage destruction, osteophyte formation, subchondral bone remodeling, and synovitis. Despite affecting millions of patients, effective and safe disease-modifying osteoarthritis drugs are lacking. Here we reveal an unexpected role for the small molecule 5-aminosalicylic acid (5-ASA), which is used as an anti-inflammatory drug in ulcerative colitis. We show that 5-ASA competes with extracellular-matrix collagen-II to bind to osteoclast-associated receptor (OSCAR) on chondrocytes. Intra-articular 5-ASA injections ameliorate OA generated by surgery-induced medial-meniscus destabilization in male mice. Significantly, this effect is also observed when 5-ASA was administered well after OA onset. Moreover, mice with DMM-induced OA that are treated with 5-ASA at weeks 8-11 and sacrificed at week 12 have thicker cartilage than untreated mice that were sacrificed at week 8. Mechanistically, 5-ASA reverses OSCAR-mediated transcriptional repression of PPARγ in articular chondrocytes, thereby suppressing COX-2-related inflammation. It also improves chondrogenesis, strongly downregulates ECM catabolism, and promotes ECM anabolism. Our results suggest that 5-ASA could serve as a DMOAD.
Topics: Humans; Male; Animals; Mice; Mesalamine; PPAR gamma; Osteoarthritis; Cartilage, Articular; Chondrocytes; Disease Models, Animal
PubMed: 38310093
DOI: 10.1038/s41467-024-45174-6 -
International Immunopharmacology Jul 2023The chronic articular disease osteoarthritis (OA) is characterized by osteophyte generation, subchondral bone remodeling, and cartilage deterioration. Low levels of H2S...
The chronic articular disease osteoarthritis (OA) is characterized by osteophyte generation, subchondral bone remodeling, and cartilage deterioration. Low levels of H2S catalyzed by cystathionine-γ-lyase (CSE) encoded by Cthhas neuroprotective, cardioprotective, anti-apoptotic, and anti-inflammatory effects thus, Cth is being developed as a potential therapy for the management of the pathogenesis and symptoms of osteoarthritis. Single-cell RNA sequencing (scRNA-seq) and immunohistochemistry of human cartilage revealed that the expression of CTH was decreased in OA patients. We found that Cthoverexpression decrease IL-1β-induced overactivation of the NF-κB signaling pathway. In vivo, Cthoverexpression relieved pain response and cartilage damage in the anterior cruciate ligament transection (ACLT) rat model. In vitro, CSE alleviated chondrocytes catabolism, inflammation, apoptosis, and senescence, and suppressed the NF-κB pathway. We postulate that CSE has therapeutic effects in suppressing inflammation and degeneration in OA and should be further investigated clinically.
Topics: Humans; Rats; Animals; NF-kappa B; Cystathionine; Cystathionine gamma-Lyase; Osteoarthritis; Inflammation; Pain; Chondrocytes; Cartilage, Articular; Disease Models, Animal
PubMed: 37182456
DOI: 10.1016/j.intimp.2023.110289 -
Biomaterials Science Jul 2023Osteoarthritis (OA) is one of the most common joint diseases currently, characterized by the gradual degradation of cartilage, remodeling of subchondral bone,... (Review)
Review
Osteoarthritis (OA) is one of the most common joint diseases currently, characterized by the gradual degradation of cartilage, remodeling of subchondral bone, development of synovitis, degenerative alterations in the menisci, and formation of osteophytes. Generally, loss of articular cartilage is the most common pathological manifestation of OA. However, owing to the lack of blood vessels and nerves, the damaged cartilage is unable to execute self-repair. Therefore, early detection and treatment of cartilage lesions are extremely vital. Given that precise diagnosis and therapeutic strategy are indispensable from the basic pathological features of OA, an ideal therapeutic strategy should cater to the specific features of the OA microenvironment to achieve disease-modifying therapy. To date, nanomedicine presents an opportunity to achieve the precisely targeted delivery of agents and stimuli-sensitive release at the optimum dose, which may be coupled with a controlled release profile and reduced side effects. This review mainly summarizes inherent and microenvironment traits of OA and outlines stimuli-responsive nanotherapies, including internal bio-responsive (, reactive oxygen species, pH, and protease) and external (, photo stimuli, temperature, ultrasound, and magnetic field) responsive nanotherapies. Furthermore, multi-targeted therapeutic strategies combined with multi-modality imaging are also discussed. In general, future exploration of more novel stimuli-responsive nanotherapies that can be used for early diagnosis and cartilage targeting may help ameliorate OA-related cartilage damage, decrease pain, and promote joint function.
Topics: Humans; Precision Medicine; Nanomedicine; Osteoarthritis; Cartilage, Articular; Multimodal Imaging
PubMed: 37305990
DOI: 10.1039/d3bm00370a -
Osteoarthritis and Cartilage Sep 2023Spinal osteoarthritis is difficult to study and diagnose, partly due to the lack of agreed diagnostic criteria. This systematic review aims to give an overview of the... (Review)
Review
OBJECTIVE
Spinal osteoarthritis is difficult to study and diagnose, partly due to the lack of agreed diagnostic criteria. This systematic review aims to give an overview of the associations between clinical and imaging findings suggestive of spinal osteoarthritis in patients with low back pain to make a step towards agreed diagnostic criteria.
DESIGN
We searched MEDLINE, Embase, Web of Science, and CINAHL from inception to April 29, 2021 to identify observational studies in adults that assessed the association between selected clinical and imaging findings suggestive of spinal osteoarthritis. Risk of bias was assessed using the Newcastle Ottawa Scale and the quality of evidence was graded using an adaptation of the GRADE approach.
RESULTS
After screening 7902 studies, 30 met the inclusion criteria. High-quality evidence was found for the longitudinal association between low back pain (LBP) intensity, and both disc space narrowing and osteophytes, as well as for the association between LBP-related physical functioning and lumbar disc degeneration, the presence of spinal morning stiffness and disc space narrowing and for the lack of association between physical functioning and Schmorl's nodes.
CONCLUSIONS
There is high- and moderate-quality evidence of associations between clinical and imaging findings suggestive of spinal osteoarthritis. However, the majority of the studied outcomes had low or very low-quality of evidence. Furthermore, clinical and methodological heterogeneity was a serious limitation, adding to the need and importance of agreed criteria for spinal osteoarthritis, which should be the scope of future research.
Topics: Adult; Humans; Osteoarthritis, Spine; Low Back Pain; Lumbar Vertebrae; Intervertebral Disc Degeneration; Intervertebral Disc Displacement
PubMed: 37150286
DOI: 10.1016/j.joca.2023.04.014 -
Biomedicines Apr 2024The increased incidence of osteoarthritis (OA), particularly knee and hip OA, and osteoporosis (OP), owing to population aging, have escalated the medical expense... (Review)
Review
The increased incidence of osteoarthritis (OA), particularly knee and hip OA, and osteoporosis (OP), owing to population aging, have escalated the medical expense burden. Osteoarthritis is more prevalent in older women, and the involvement of subchondral bone fragility spotlights its association with OP. Notably, subchondral insufficiency fracture (SIF) may represent a more pronounced condition of OA pathophysiology. This review summarizes the relationship between OA and OP, incorporating recent insights into SIF. Progressive SIF leads to joint collapse and secondary OA and is associated with OP. Furthermore, the thinning and fragility of subchondral bone in early-stage OA suggest that SIF may be a subtype of OA (osteoporosis-related OA, OPOA) characterized by significant subchondral bone damage. The high bone mineral density observed in OA may be overestimated due to osteophytes and sclerosis and can potentially contribute to OPOA. The incidence of OPOA is expected to increase along with population aging. Therefore, prioritizing OP screening, early interventions for patients with early-stage OA, and fracture prevention measures such as rehabilitation, fracture liaison services, nutritional management, and medication guidance are essential.
PubMed: 38672197
DOI: 10.3390/biomedicines12040843 -
Journal of Nanobiotechnology Oct 2023Osteoarthritis (OA) is a prevalent joint disease that affects all the tissues within the joint and currently lacks disease-modifying treatments in clinical practice....
Osteoarthritis (OA) is a prevalent joint disease that affects all the tissues within the joint and currently lacks disease-modifying treatments in clinical practice. Despite the potential of rapamycin for OA disease alleviation, its clinical application is hindered by the challenge of achieving therapeutic concentrations, which necessitates multiple injections per week. To address this issue, rapamycin was loaded into poly(lactic-co-glycolic acid) nanoparticles (RNPs), which are nontoxic, have a high encapsulation efficiency and exhibit sustained release properties for OA treatment. The RNPs were found to promote chondrogenic differentiation of ATDC5 cells and prevent senescence caused by oxidative stress in primary mouse articular chondrocytes. Moreover, RNPs were capable to alleviate metabolism homeostatic imbalance of primary mouse articular chondrocytes in both monolayer and 3D cultures under inflammatory or oxidative stress. In the mouse destabilization of the medial meniscus (DMM) model, intra-articular injection of RNPs effectively mitigated joint cartilage destruction, osteophyte formation, chondrocytes hypertrophy, synovial inflammation, and pain. Our study demonstrates the feasibility of using RNPs as a potential clinically translational therapy to prevent the progression of post-traumatic OA.
Topics: Mice; Animals; Sirolimus; Cartilage, Articular; Osteoarthritis; Disease Models, Animal; Nanoparticles
PubMed: 37794470
DOI: 10.1186/s12951-023-02118-4 -
Frontiers of Medicine Apr 2024Osteoarthritis (OA) is a degenerative bone disease associated with aging. The rising global aging population has led to a surge in OA cases, thereby imposing a... (Review)
Review
Osteoarthritis (OA) is a degenerative bone disease associated with aging. The rising global aging population has led to a surge in OA cases, thereby imposing a significant socioeconomic burden. Researchers have been keenly investigating the mechanisms underlying OA. Previous studies have suggested that the disease starts with synovial inflammation and hyperplasia, advancing toward cartilage degradation. Ultimately, subchondral-bone collapse, sclerosis, and osteophyte formation occur. This progression is deemed as "top to bottom." However, recent research is challenging this perspective by indicating that initial changes occur in subchondral bone, precipitating cartilage breakdown. In this review, we elucidate the epidemiology of OA and present an in-depth overview of the subchondral bone's physiological state, functions, and the varied pathological shifts during OA progression. We also introduce the role of multifunctional signal pathways (including osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL)/receptor activator of nuclear factor-kappa B (RANK), and chemokine (CXC motif) ligand 12 (CXCL12)/CXC motif chemokine receptor 4 (CXCR4)) in the pathology of subchondral bone and their role in the "bottom-up" progression of OA. Using vivid pattern maps and clinical images, this review highlights the crucial role of subchondral bone in driving OA progression, illuminating its interplay with the condition.
Topics: Humans; Osteoarthritis; Disease Progression; Osteoprotegerin; Bone and Bones; RANK Ligand; Signal Transduction; Cartilage, Articular; Chemokine CXCL12; Receptors, CXCR4; Receptor Activator of Nuclear Factor-kappa B
PubMed: 38619691
DOI: 10.1007/s11684-024-1061-y